The present application is generally directed to a process for the synthesis of fusarochromanone (FC) and analogs thereof, as well as certain intermediates useful in such syntheses.
Members of the Fusarium species are distributed worldwide as soil inhabitants and parasites of cultivated plants. Some isolates of the species are capable of producing mycotoxins, the ingestion of which has been associated with a variety of animal intoxications. For example, chicks fed diets containing a 5% level of crude fungus cultures from Fusarium equiseti develop a syndrome known as Avian Tibial Dyschondroplasia (ATD), characterized by bone deformation and failure of cartilage calcification (Walser et al., 1982, Vet Pathol 19: 544-550).
Fusarochromanone (“FC”) is a water soluble component derived from Fusarium cultures. Fusarochromanone has been purified and characterized (Pathre et al., 1986, Can. J. Chem 64: 1308-1311), and one form of this compound, designated FC101 and having the chemical formula 5-amino-2,2-dimethyl-6-[3′-(R,S)amino-4′-hydroxy-butan-1-one]-2,3-dihydro-4H-1-benzopyran-4-one, has been shown to cause ATD when administered to day-old broiler chicks (Lee et al., 1985, Appl. Environ. Microbiol. 50:102-107).
Fusarochromanone is a biologically active compound; it is an inhibitor of angiogenesis, which is the development of new blood vessels from existing capillaries. Certain angiogenesis inhibitors have been suggested for use in therapies for cancer, rheumatoid arthritis, psoriasis, Kaposi's Sarcoma, ischemic heart disease, atherosclerosis and ocular diseases, such as diabetic retinopathy, involving retinal vessel proliferation.